Field of the Invention
The present invention relates generally to small molecules for the treatment of neurological disorders and, more specifically, to methods for the prevention of Parkinson's Disease (PD) or preventing its progression in a subject with PD.
Background Information
Parkinson's disease is a common neurodegenerative disorder characterized clinically by bradykinesia, rigidity, tremor, and gait dysfunction, and pathologically by degeneration of dopamine neurons in the substantia nigra pars compacta (SNc) and projecting to the striatum (including the putamen).
There is no known cure for PD. Patients are treated with drugs and physical therapy to control the symptoms, but the disease is a progressive disorder and symptoms continue to worsen throughout life. There are four major categories of drugs used to treat PD: Levodopa, direct dopamine agonists, catechol-O-methyltransferase (COMT) inhibitors and anticholinergics. Other types of drugs include selegiline (an MAO-B inhibitor), amantadine (an antiviral agent), vitamin E and hormone replacement therapy. Although these treatments may provide some relief from the symptoms of PD, these noncurative drug treatments are often are accompanied by side effects, such as low blood pressure, nausea, constipation, and various psychiatric or behavioral disorders (e.g., hallucinations, depression, and sleep disorders). Present therapies provide satisfactory disease control for most patients, particularly in the early stages. However, no treatments protect against the continued degeneration of these neurons and, over time, all therapies fail. Chronic levodopa treatment is associated with motor complications, does not control potentially disabling features such as falling and dementia, and fails to prevent disease progression. (Olanow et al., Neurology 72: suppl 4:S1-S136 (2009)). Thus, many patients suffer disability despite available medical and surgical treatments. More effective treatments that improve clinical disease control and slow progression are urgently needed.